Sunday , April 11 2021

Goodbye to the syringes: researchers from the CONICET design a new platform to develop oral vaccines

Goodbye to the syringes: researchers from the CONICET design a new platform to develop oral vaccines

A platform designed by a computer of the CONICET and directed by the researcher Hugo Luján in Córdoba, was created to develop oral vaccines and replace the use of syringes, was recently published in the journal Nature Communication.

In many people vaccinate it triggers fears, because behind the syringe tends to appear injections, worries about the needle sterility or the ghost of getting a cross infection.

Hugo Luján, doctor in Chemical Sciences of the National Council of Scientific and Technical Investigations (CONICET) And director of Center for Research and Development in Immunology and Infectious Diseases (CIDIE) in Córdoba, He designed a cure for all these evils: a platform that would allow any antigen to be converted into an oral intake vaccine, which could be replaced by traditional injections and would mean the end of nightmare.

To this day, the only oral vaccine that exists in the market is the I knew, Which was developed in the 60s and is applied against Poliomelitis in children 6 months to 5 years of age. The platform developed by Luján, recently published through the publication of a paper in the journal Nature Communications, could be used in the generation of oral vaccines that fight any infectious agent, even against tumor cells.

Of course, the emergence of this development is behind a chain of previous developments and more than twenty years of dedication to the study of the mechanisms for the adaptation of human and animal pathogenic parasites. To understand this, you should first review how traditional vaccines work. The mechanism is very simple: through an injection, a small amount of viruses or bacteria enter the body that "teach" the immune system to recognize, defend and attack microorganisms -virus or bacteria- when eventually invade it

In contrast to injectable vaccines, the main disadvantage of oral vaccines is that they can easily degrade to the intestine through digestion. However, Luján and his team were pioneers in generating, in 2008, an oral vaccine against Giardiasis, a diarrheal disease that mainly affects underdeveloped countries, caused by a unicellular microscopic parasite that lives in the # 39; The small intestine of people and is transmitted by the feces of an infected person or animal.

How did they come to this discovery? The Giardia lambia parasite is particular, because it has an adaptive mechanism called "antigenic variation", which acts as a "disguise": through this process, the parasite has the ability to continuously change its main surface molecules ( called "variable surface proteins" or VSPs), which allows it to evade the host's immune response and therefore can remain chronically in the intestine of a person or animal. That is why, too, Giardia was a parasite so difficult to fight. Luján obtained, for the first time, that the complete repertoire of purified native VSPs was capable of causing a protective immune response against all possible "costumes" of the parasite in an oral way, which was validated in the laboratory and then in domestic animals, with results that allowed CONICET its licensing to an international company.

With this patented development, Luján met with colleagues from France and a new idea arose: to develop oral vaccines to prevent other infectious agents, attaching to the antigens the VSPs proteins of Giardia, which due to their protective properties would allow vaccines Oral resists in the intestine and are not degraded. French colleagues, in turn, contributed the development of "virus-like particles" (VLPs), particles that stimulate the immune system to mimic the structures of viruses, but do not have their genetic material, so do not get sick. The decoration of surfaces of VLPs with VSPs and antigens that are wanted to fight – such as the flu, by Zika, of tuberculosis – resulted in effective oral vaccines in animal studies. This combination is the revolutionary platform created by Luján with his colleagues and his team, with special participation by the researchers Marianela Serradell and Lucía Rupil.

Development details

"The virus-like particles are like the casing, to which I add any molecule, to generate an immune response against it. But at the same time it adds the Giardia surface proteins to protect them from the intestine. Giardia lives in the intestine and nobody knew why it was not digested like any food, we started to see these surface proteins that helped us to build this vaccine against Giardia, and we saw that if we put them out, these particles similar to viruses did not degrade, "Luján explains. "Although it seems complex, it is an easy technique to carry out and without the need for high complexity equipment," says the researcher at CONICET.

"We produced these proteins from Giardia in the laboratory, we underwent different conditions of digestion, and we see that all these proteins resist, then they are excellent to protect these viral particles, which we can attach to any vaccine antigen. the platform, "he adds. "We have already tested it with influenza virus antigens, the respiratory syncytial virus, tuberculosis and Zika, and these antigens do not degrade and generate an important immune response not only in the mucous membranes, because most of the Infectious agents, but also systemically. "

Luján adds that "during our studies we also observed that injecting mice vaccinated against a certain antigen and tumor cells expressing this specific antigen, the tumors were not developed, which did occur in non-vaccinated animals or in those vaccinated orally with particles without VSPs. Even for some tumors the vaccine worked therapeutically. "

Among the advantages of oral vaccines, Luján points out that "how these oral particles do not require cold for transport or storage because they include Giardia proteins – which supports changes in temperature and pH both inside and outside the intestine- They do not require a cold chain or any particular logistics. Neither do they need trained personnel, they do not present a risk of cross-infection, avoid the risks associated with the use of syringes and needles, they do not have costs for discarding, they are painless and When constituting a non-invasive technique they are attractive for their application in massive or personalized vaccination programs. "

For Luján, "the possibilities that are opened with this platform are immense and we can generate significant resources for the country." And he concludes: "We never imagined that we were going to find it helpful to these proteins beyond the Giardia vaccine. Science is like this: one can not predict what it is going to end. The next step is for clinical trials in beings humans ".

comparative trials

In the essays, "the fundamental thing that we discovered is that once we mumble our mice with these viral particles containing flu virus antigens, very easy to generate and cheap in the laboratory, it happened that these antigens were not degraded Then we saw that our proteins protected the degradation particles. On the other side, we saw that they activated the immune system by binding to a specific receptor (the TLR-4 receptor), and once vaccinated, we measured His response: the mice that were vaccinated orally were protected against the virus challenge by 100 percent, while mice that were vaccinated by the injectable route were protected by 80 percent. Then we demonstrated that the Our oral vaccine, to be vaccinated through the upper intestine, not the large intestine, was better than vaccinating with an injection. "

With this response, they used the platform for therapeutic vaccines against different types of cancer. "I am divagging, making futurism according to the results, that we have only animals, but that opens the door for these studies, for example those of cancer, because once they detect a tumor, a biopsy is made and it's analyzed, you know what specific antigens a person needs, and with this system we could do a personalized vaccine for each patient, "Luján advances.


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